title: Trastuzumab-related cardiotoxicity in early breast cancer: a cohort study.
abstract: BACKGROUND
  Concerns have been raised about the cardiac safety profile of trastuzumab for the adjuvant treatment of early stage breast cancer in clinical practice. We assessed trastuzumab-related cardiotoxicity and its predictors in a large cohort of Italian women.
  
  
  METHODS
  Through a record linkage between four regional health care databases, we identified the rate of severe cardiac adverse events among women treated with trastuzumab for early breast cancer in Lombardy. The cumulative risk of cardiotoxicity was estimated using the Kaplan-Meier method, and independent predictors were assessed using the Cox model.
  
  
  RESULTS
  Of 2,046 trastuzumab users, 53 (2.6%) experienced at least one hospitalization for a cardiac event, and there were two cardiac deaths. The cumulative risk of cardiotoxicity increased up to 2 years after starting treatment, reaching a plateau at 2.8%. The risk was low (0.2%) among young women, whereas the incidence was approximately 10% in women aged ≥70 years, irrespective of cardiovascular risk factors. Age and history of cardiac disease were strong predictors of cardiotoxicity, with a hazard ratio of 11.3 (95% confidence interval [CI]: 3.5-36.6) for women aged ≥70 years as compared with those <50 years of age. Hazard ratio was 4.4 (95% CI: 2.1-9.5) for women with a history of cardiac disease compared with those without a history of cardiac disease.
  
  
  CONCLUSIONS
  Cardiotoxicity of trastuzumab varies considerably across subgroups of patients. The long-term safety profile was less favorable than in the largest clinical trial. Strategies to reduce cardiotoxicity in high-risk women should be investigated.
authors.affiliation: Department of Epidemiology, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Bonifazi
authors.forename: Matteo
authors.initials: M
authors.lastname: Franchi
authors.forename: Marta
authors.initials: M
authors.lastname: Rossi
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moja
authors.forename: Alberto
authors.initials: A
authors.lastname: Zambelli
authors.forename: Antonella
authors.initials: A
authors.lastname: Zambon
authors.forename: Giovanni
authors.initials: G
authors.lastname: Corrao
authors.forename: Carlo
authors.initials: C
authors.lastname: La Vecchia
authors.forename: Carlo
authors.initials: C
authors.lastname: Zocchetti
authors.forename: Eva
authors.initials: E
authors.lastname: Negri
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D015331:Cohort Studies; D018572:Disease-Free Survival; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced* / Q000209:etiology / Q000401:mortality / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068878:Trastuzumab
keywords: Adjuvant chemotherapy; Cardiotoxicity; Early breast cancer; Survival; Trastuzumab